Weaver Mouse Cerebellum Research Articles

Possible synapse formation by embryonic cerebellar tissue grafted into the cerebellum of the weaver mutant mouse.

The weaver mutant mouse is characterized by degeneration of cerebellar granule cells in early post-natal stage. In the present study, the possibility of synapse formation in the weaver mouse cerebellum by implanted granule cells was analyzed immunohistochemically with antiserum against synaptic vesicle protein, Synapsin I. Normal cerebellar tissue, obtained from 15-day-old CBA/JNCij mouse embryos, was transplanted into the cerebellum of 4-week-old weaver mice. 6 weeks after the transplantation, the grafted tissue was clearly detected in the host cerebellum, developing a trilaminar organization. A number of granule-like cells were observed in the folia of the host cerebellum, suggesting that the implanted granule cells may have migrated from the grafted tissue into the host cerebellum. Some areas in the host cerebellum as well as in the grafted tissue were intensely stained by anti-Synapsin I serum, indicating that the implanted granule cells make synaptic contacts with the neuronal cells.

Granule cell as a site of gene action in the weaver mouse cerebellum: evidence from heterozygous mutant chimeras

Experimental mouse chimeras were used to determine the site(s) of gene action in the weaver mutant cerebellum. Chimeras containing mixtures of heterozygous weaver (wv/+) and non-weaver (+/+) cells were produced by the standard embryo aggregation technique. The non-weaver component of the chimera was chosen so that Purkinje cells or granule cells could be distinguished histologically from weaver Purkinje or granule cells. Levels of beta-glucuronidase activity were used to mark Purkinje cells, with the weaver strain having a high beta-glucuronidase activity, while the non-weaver strain had low beta-glucuronidase activity. The increased centralized clumping of heterochromatin in ichthyosis (ic) mutant mice compared to non-ic mice was used to mark granule cell populations. In the weaver chimera, there was a decreased cerebellar size, decreased numbers of Purkinje and granule cells, and increased ectopic Purkinje and granule cells compared to non-weaver, control mice. With the glucuronidase cell marker, it was found that there was no correlation between ectopia and genotype; that is, genetically normal cells, as well as weaver cells, were found in ectopic positions. Thus, the weaver gene acts extrinsic to the Purkinje cells in creating the ectopia characteristic of heterozygous weaver mutants. Analysis of the ectopic granule cells, however, revealed that 100% of the ectopic granule cells were from the weaver component of the chimera. Thus, the weaver gene intrinsically affects granule cells in causing ectopia. Other hypothetical sites of gene action would produce a genetically mixed population of ectopic granule cells, which was not the case in this study. These findings are discussed in relation to other abnormalities in the heterozygous weaver mutant and in regard to the Bergmann glia and homozygous mutant. Finally, speculations on the nature of the granule cell deficit are discussed briefly.

Dendro-dendritic pentalaminar junctions in the Weaver mouse cerebellum.

The cerebellum of weaver mouse is characterized by an extensive reorganization of cell interaction secondary to the absence of mature granule cells. One yet undescribed modality of reorganization found in the hemispheres of 1-month-old animals consisted in the presence of dendro-dendritic pentalaminar junctions. The possible formation of these junctions by fusion of facing post-synaptic densities is discussed.

Membrane specializations of dentritic spines and glia in the weaver mouse cerebellum: a freeze-fracture study.

Electron microscopy of thin-sectioned and freeze-fractured preparations of the cerebellum of the weaver mouse indicates that the dendritic spines are morphologically identical to those of their normal littermates. The weaver dendritic spines have been characterized as "unattached" since the synaptic input from the parallel fibers is absent (8-10). The entire region around the dendritic spines is taken up by astrocytic processes in the weaver. The outer fracture face of a normal dendritic spine contains aggregations of 10-nm wide particles in the immediate postsynaptic region. Similar particle aggregations occur in the unattached spines of the weaver. Freeze-fracture preparations reveal rectilinear arrays of particles, having a 7-nm center-to-center distance in the glial membranes. Rectilinear arrays are apparently distributed throughout the astrocyte membrane.

Glutamic acid: A strong candidate as the neurotransmitter of the cerebellar granule cell

Free amino acids and cholinergic enzymes were investigated in the cerebellum of reeler and weaver mice in an attempt to identify the neurotransmitter characteristic of the granule cell population and to clarify any neurotransmitter abnormalities of their pre- and postsynaptic neurons induced by their depletion. The data indicate that glutamic acid may be the neurotransmitter of the granule cells. Pre- and postsynaptic neurotransmitter activity seemed not to be markedly altered in cerebellar granule cell dysgenesis.

Observations on the development of the Weaver mouse cerebellum.

The cerebellar cortices of young weaver mice were examined by electron microscopy and compared with those of normal littermates. Unattached dendritic spines arising from Purkinje cells, very much like those previously described in the adult weaver, were found by the eleventh day after birth. Granule cell degeneration was seen but not examples of degeneration of presynaptic structures could be detected. Unlike either the adult weaver or the developing normal mouse, symmetrical junctions between dendritic spines were present, as were asymmetrical junctions between Purkinje cell dendritic spines and nonspecialized regions of the surface of external granule cell soma. The mechanism of formation of the unattached spines is discussed.

Cerebellar alterations in the weaver mouse.

The fine structure of the cerebellum of weaver mouse was examined and the paucity of granule cells and their axons, the parallel fibers, was confirmed. Unexpectedly, however, the dendritic spines of the Purkinje cells which, in normal animals, are the postsynaptic mates of the parallel fibers, were present. Furthermore, their essential morphology and their staining reactions were indistinguishable from those of the Purkinje cell dendritic spines in normal animals. Possible mechanisms of development are discussed.